CLL / SLLPhase 2ZSNCT07682415
Zanubrutinib Induction Followed by Delayed Fixed-Duration Combination With Sonrotoclax for CLL/SLL：Stop Trial 2.0
A Phase 2 study testing 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax and zanubrutinib maintenance until disease progression in people with CLL / SLL, run by Yi Shuhua at 7 sites in China.
Trial summary
The goal of this clinical trial is to learn if zanubrutinib induction followed by delayed fixed-duration combination with sonrotoclax works to treat previously untreated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL). It will also learn about the safety of this combination regimen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CLL / SLL
- What is being tested?
- 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax and zanubrutinib maintenance until disease progression
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 7 sitesChina
- Study dates
- 8 Jun 2026to 1 Aug 2034
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥18 years, no restriction on gender.
- Newly diagnosed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) consistent with the Chinese Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (2025 Edition).
- Meet at least one of the following indications for CLL treatment:
- Evidence of progressive bone marrow failure manifested by progressive reduction in hemoglobin and/or platelet counts.
- Massive splenomegaly (spleen palpable >6 cm below the left costal margin) or symptomatic splenomegaly.
- Bulky lymphadenopathy (maximum diameter >10 cm) or symptomatic lymphadenopathy.
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- Progressive lymphocytosis: ≥50% increase in lymphocyte count within 2 months, or lymphocyte doubling time (LDT) <6 months. LDT alone shall not serve as an indication for treatment if the baseline lymphocyte count is <30×10⁹/L.
- Symptomatic organ dysfunction caused by CLL/SLL (involving skin, kidney, lung, spine and other organs).
- Autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) with inadequate response to corticosteroid therapy.
- At least one of the following disease-related B symptoms:
- Unintentional weight loss ≥10% within the preceding 6 months without identifiable cause; ② Severe fatigue (ECOG performance status ≥2, inability to perform routine daily activities);
- ③ Unexplained fever >38.0 °C lasting ≥2 weeks without confirmed infection;
- ④ Unexplained night sweats persisting for more than 1 month without confirmed infection.
- ECOG performance status ≤2.
- Major organ function meets the following criteria within 7 days prior to treatment initiation:
- ￮ Hematology: platelet count ≥30×10⁹/L;
- ￮ Biochemistry: total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; creatinine clearance ≥30 mL/min;
- ￮ Cardiac Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥lower limit of normal (50%).
- Male and female participants agree to use effective contraception throughout the study period and for a minimum of 4 weeks after treatment completion.
- Estimated life expectancy ≥6 months.
- The patient voluntarily participates in the trial and signs the written informed consent form.
Who cannot join
- 1. Previously received any systemic anti-tumor therapy for CLL/SLL. 2. Pathologically confirmed transformation to Richter's syndrome via biopsy. 3. Severe non-lymphoma-related hepatic or renal impairment defined as: ALT/AST >3×ULN or TBIL >2×ULN; creatinine clearance <30 mL/min or serum creatinine >2×ULN.
- 4. Significant pre-existing renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular or hepatic disease judged by the investigator to compromise trial participation.
- 5. Other uncontrolled clinically significant medical conditions including but not limited to:
- Uncontrolled systemic infection (viral, bacterial, fungal); positive hepatitis B surface antigen with HBV-DNA >1000 IU/mL; positive anti-HCV antibody or detectable HCV-RNA; positive anti-HIV antibody.
- Active uncontrolled autoimmune diseases other than autoimmune cytopenias. 6. Clinical signs of central nervous system (CNS) dysfunction or documented CNS infiltration by disease.
- 7. Received major surgery (excluding lymph node biopsy) within 14 days prior to enrollment or scheduled to undergo major surgery during trial treatment.
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- 8. Inability to swallow capsules, malabsorption syndrome, or severe gastrointestinal disorders including prior gastrectomy, small bowel resection, symptomatic inflammatory bowel disease, ulcerative colitis, partial or complete intestinal obstruction.
- 9. Concurrent use of strong CYP3A inhibitors or inducers during study drug initiation and dose titration period.
- 10. Pregnant or breastfeeding females; females of childbearing potential without reliable contraceptive measures.
- 11. Clinically significant cardiovascular disease (NYHA cardiac functional class III/IV); history of myocardial infarction, malignant arrhythmia (including QTc ≥480 ms), inadequately controlled hypertension (systolic BP ≥150 mmHg, diastolic BP ≥100 mmHg) or unstable angina within 6 months before enrollment.
- 12. Coagulopathy-related exclusion: long-term treatment with multiple high-dose anticoagulants with no possibility of short-term discontinuation; persistent uncontrolled active bleeding; or prior life-threatening irreversible bleeding events.
- 13. History of severe hypersensitivity to any active ingredient or excipient of the investigational product.
- 14. Systemic disorders that may impair patient compliance with trial requirements.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Tingyu Wang, Doctor contact
7 sites in 1 country
China7 sites
The Second Xiangya Hospital of Central South University
Changsha, Hunan
hongling peng, （+86）18900766137, 577769365@qq.com
Qilu Hospital of Shandong University
Jinan, Shandong
jingjing ye, （+86）18560086995, yejingjing@sdu.edu.cn
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi
fei li, （+86）13970038386, yx021021@sina.com
Jiangsu Province Hospital
Nanjing, Jiangsu
huayuan zhu, （+86）13813810650, huayuan.zhu@hotmail.com
Shenzhen Second People's Hospital
Shenzhen, Guangdong
xiaoqing li, （+86）18620385718, 18620385718@163.com
Blood Disease Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, CAMS)
Tianjin, Tianjin Municipality, 300000
Shuhua Yi, Doctor, （+86）15900265415, yishuhua@ihcams.ac.cn
Tingyu Wang, Doctor, wangtingyu@ihcams.ac.cn
Henan Cancer Hospital
Zhengzhou, Henan
keshu zhou, （+86）13674902391, dr_zkshu23810@163.com
About this study
Official title: A Single-arm, Multicenter, Prospective Phase II Clinical Trial of Delayed Fixed-duration Combination With Sotoraclax Following Zanubrutinib Induction in Patients With CLL/SLL: Stop Trial 2.0
The goal of this clinical trial is to learn if zanubrutinib induction followed by delayed fixed-duration combination with sonrotoclax works to treat previously untreated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL). It will also learn about the safety of this combination regimen. The main questions it aims to answer are:Does this combination therapy achieve undetectable minimal residual disease (uMRD) in participants?What medical problems (adverse events) do participants have when taking zanubrutinib and sonrotoclax?Researchers will conduct a single-arm study to systematically evaluate the MRD clearance, efficacy, safety, and immune-related functions of this specific treatment sequence.Participants will:Low-risk group (without 17p deletion/TP53 mutation): Take zanubrutinib monotherapy for 12 cycles, followed by combination zanubrutinib + sonrotoclax for 12 cycles, then discontinue treatment for observation.High-risk group (with 17p deletion/TP53 mutation): Follow the same initial regimen (12 cycles monotherapy + 12 cycles combination), followed by zanubrutinib monotherapy maintenance until disease progression.Visit the clinic periodically for MRD assessment (via flow cytometry), efficacy evaluation (CT/PET-CT, lab tests), and safety checks (physical exam, blood tests, ECG).Undergo immune function evaluation via peripheral blood samples to assess changes in T-cell counts and subsets.
Read the detailed description
This exploratory Phase II single-arm clinical trial is designed to evaluate the efficacy, safety, and immune reconstitution effects of a novel delayed fixed-duration BTK inhibitor (BTKi) induction followed by BCL-2 inhibitor combination regimen in previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients, with risk-stratified post-treatment management based on TP53/del(17p) status.Scientific RationaleCLL/SLL is a mature B-cell clonal proliferative neoplasm, where traditional chemoimmunotherapy has limited efficacy and high toxicity in high-risk populations with del(17p)/TP53 mutations. The current treatment paradigm has shifted to targeted therapies, with BTKi + BCL-2i combination as a first-line strategy. However, existing BCL-2i-based fixed-duration regimens have a grade ≥3 treatment-emergent adverse event (TEAE) incidence of 45%-80%, primarily hematological toxicities and infections. Prior clinical evidence shows that 12 cycles of BTKi monotherapy induction before combination therapy (the "brake" regimen) reduces infection risk compared to alternating chemoimmunotherapy + BTKi regimens, and 12 months of BTKi monotherapy increases T-cell receptor diversity, correlating with better clinical response and lower infection rates in relapsed/refractory CLL. This supports that extending BTKi induction before fixed-duration BCL-2i combination may optimize immune reconstitution, improving safety and long-term disease control.The study uses two investigational agents: zanubrutinib, a next-generation highly selective BTKi with higher BTK target selectivity and fewer off-target effects (e.g., lower cardiovascular adverse event risk vs. first-generation ibrutinib) compared to ibrutinib, approved in China for relapsed/refractory CLL/SLL and mantle cell lymphoma (MCL); and sonrotoclax, a highly selective BCL-2 inhibitor that restores mitochondrial apoptosis in CLL cells, with monotherapy showing 80.5% ORR and 26.8% CR/CRi rate in BTKi-pretreated high-risk relapsed/refractory CLL, and zanubrutinib + sonrotoclax combination achieving 92% 48-week uMRD rate and 100% 30-month PFS rate in treatment-naïve CLL/SLL. Study Design and PopulationThe study will consecutively enroll approximately 60 treatment-naïve CLL/SLL subjects meeting the 2025 Chinese CLL/SLL Diagnosis and Treatment Guidelines criteria, stratified into two groups:High-risk group (n=20): With 17p deletion (del17p) and/or TP53 mutationLow-risk group (n=40): Without del17p and/or TP53 mutationLow-risk group: Discontinue all treatment and enter observational follow-upHigh-risk group: Receive zanubrutinib monotherapy maintenance until disease progressionThis protocol is designed to systematically evaluate whether the delayed BCL-2i combination after extended BTKi induction improves MRD clearance, reduces toxicity, and optimizes long-term outcomes in treatment-naïve CLL/SLL, with tailored post-treatment management for high-risk populations to address their higher relapse risk.
- Conditions
- CLL / SLL
- Being tested
- 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax, zanubrutinib maintenance until disease progression
- Keywords
- Zanubrutinib, Sonrotoclax, Chronic Lymphocytic Leukemia
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclaxDrug
12 cycles of zanubrutinib monotherapy induction → 12 cycles of zanubrutinib combined with sonrotoclax → discontinuation of study drugs followed by regular follow-up Zanubrutinib Dosage The total daily oral dose is 320 mg. The dosing schedule is 160 mg (2 × 80 mg capsules) twice daily, Sonrotoclax Dose Escalation Schedule
Cycle 13 Week 1 (C13W1):
Days 1-3: 1 mg daily (1 × 1 mg tablet); Days 4-7: 2 mg daily (2 × 1 mg tablets)
Cycle 13 Week 2 (C13W2):
Days 1-3: 5 mg daily (1 × 5 mg tablet); Days 4-7: 10 mg daily (2 × 5 mg tablets)
Cycle 13 Week 3 (C13W3):
Days 1-3: 20 mg daily (1 × 20 mg tablet); Days 4-7: 40 mg daily (2 × 20 mg tablets)
Cycle 13 Week 4 (C13W4):
Days 1-3: 80 mg daily (1 × 80 mg tablet); Days 4-7: 160 mg daily (2 × 80 mg tablets) Cycle 14 Week 1 (C14W1) and all subsequent cycles: 320 mg daily (4 × 80 mg tablets)
zanubrutinib maintenance until disease progressionDrug
Continuous zanubrutinib monotherapy until disease progression or intolerable toxicity occurs.
| Study group | Role | What they receive |
|---|---|---|
| Low-risk group（Without del17p and/or TP53 mutation） | Experimental | 12 cycles of zanubrutinib monotherapy induction → 12 cycles of zanubrutinib combined with sonrotoclax → discontinuation of study drugs followed by regular follow-up Receives: Drug: 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax |
| High-risk group(With del17p and/or TP53 mutation) | Experimental | 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax, then zanubrutinib maintenance monotherapy until disease progression or intolerable toxicity occurs. Receives: Drug: 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax; Drug: zanubrutinib maintenance until disease progression |
What is being measured
The primary outcome is the main question the study is designed to answer.
uMRD rate
Proportion of patients achieving undetectable minimal residual disease (uMRD, defined as MRD <10-⁴, fewer than 1 CLL cell per 10,000 leukocytes)
Measured: At the end of 12 cycles (each cycle is 28 days) of combination therapy
Secondary outcomes (5)
Objective Response Rate
The proportion of patients who achieve a Complete Response (CR) and a Partial Response (PR) according to standardized criteria
Measured: At the end of 12 cycles (each cycle is 28 days) of combination therapy
Complete Response Rate
The percentage of patients who meet the stringent criteria for Complete Remission
Measured: At the end of 12 cycles (each cycle is 28 days) of combination therapy
Duration of Response
The time from the first documented objective response (CR or PR) until disease progression (PD) or death from any cause.
Measured: up to 8 years
Progression-Free Survival
The time from treatment initiation (or randomization) to disease progression or death
Measured: up to 8 years
Overall Survival
The time from treatment initiation (or randomization) to death from any cause
Measured: up to 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2026
- Study start8 Jun 2026 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion1 Aug 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for CLL / SLLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yi Shuhua
- Sponsor type
- University, hospital or other
- Collaborators
- BeOne Medicines
- Responsible party
- Sponsor-investigator, Yi Shuhua, Institute of Hematology & Blood Diseases Hospital, China
- Investigators
- Shuhua Yi, Docter, Principal investigator, Blood Disease Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, CAMS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07682415
- Sponsor's protocol ID
- IIT2026068
- Acronym
- ZS
- Status last verified
- Jun 2026
- First submitted
- 2 Jun 2026
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: only IPD used in the results publication
Publications
Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984 Nov 30;226(4678):1097-9. doi: 10.1126/science.6093263.
PubMed 6093263Hugosson J, Mansson M, Wallstrom J, Axcrona U, Carlsson SV, Egevad L, Geterud K, Khatami A, Kohestani K, Pihl CG, Socratous A, Stranne J, Godtman RA, Hellstrom M; GOTEBORG-2 Trial Investigators. Prostate Cancer Screening with PSA and MRI Followed by Targeted Biopsy Only. N Engl J Med. 2022 Dec 8;387(23):2126-2137. doi: 10.1056/NEJMoa2209454.
PubMed 36477032Venditti A, Piciocchi A, Candoni A, Melillo L, Calafiore V, Cairoli R, de Fabritiis P, Storti G, Salutari P, Lanza F, Martinelli G, Luppi M, Mazza P, Martelli MP, Cuneo A, Albano F, Fabbiano F, Tafuri A, Chierichini A, Tieghi A, Fracchiolla NS, Capelli D, Foa R, Alati C, La Sala E, Fazi P, Vignetti M, Maurillo L, Buccisano F, Del Principe MI, Irno-Consalvo M, Ottone T, Lavorgna S, Voso MT, Lo-Coco F, Arcese W, Amadori S. GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia. Blood. 2019 Sep 19;134(12):935-945. doi: 10.1182/blood.2018886960. Epub 2019 Aug 8.
PubMed 31395600Bischler T, Hsieh PK, Resch M, Liu Q, Tan HS, Foley PL, Hartleib A, Sharma CM, Belasco JG. Identification of the RNA Pyrophosphohydrolase RppH of Helicobacter pylori and Global Analysis of Its RNA Targets. J Biol Chem. 2017 Feb 3;292(5):1934-1950. doi: 10.1074/jbc.M116.761171. Epub 2016 Dec 14.
PubMed 27974459Chriskos P, Frantzidis CA, Plomariti CS, Papanastasiou E, Pataka A, Kourtidou-Papadeli C, Bamidis PD. SmartHypnos: An Android application for low-cost sleep self-monitoring and personalized recommendation generation. Comput Biol Med. 2025 Jan;184:109306. doi: 10.1016/j.compbiomed.2024.109306. Epub 2024 Nov 14.
PubMed 39541899Laurencin CT, Walker JM. A Pandemic on a Pandemic: Racism and COVID-19 in Blacks. Cell Syst. 2020 Jul 22;11(1):9-10. doi: 10.1016/j.cels.2020.07.002. Epub 2020 Jul 22.
PubMed 32702320Jana A, Baruah M, Munan S, Samanta A. ICT based water-soluble fluorescent probe for discriminating mono and dicarbonyl species and analysis in foods. Chem Commun (Camb). 2021 Jun 29;57(52):6380-6383. doi: 10.1039/d1cc02600c.
PubMed 34081065Zakir M, Thomas D, Adams R, Farnell D, Claydon N. A Systematic Review and Meta-Analysis of the Clinical Outcomes for Adjunctive Physical, Chemical, and Biological Treatment of Dental Implants With Peri-Implantitis. J Oral Implantol. 2023 Apr 1;49(2):168-178. doi: 10.1563/aaid-joi-D-21-00204.
PubMed 37071563Duncanson G. Evolve to thrive. Vet Rec. 2019 May 4;184(18):560. doi: 10.1136/vr.l1956. No abstract available.
PubMed 31048528Tam CS, Allan JN, Siddiqi T, Kipps TJ, Jacobs R, Opat S, Barr PM, Tedeschi A, Trentin L, Bannerji R, Jackson S, Kuss BJ, Moreno C, Szafer-Glusman E, Russell K, Zhou C, Ninomoto J, Dean JP, Wierda WG, Ghia P. Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort. Blood. 2022 Jun 2;139(22):3278-3289. doi: 10.1182/blood.2021014488.
PubMed 35196370Eichhorst B, Ghia P, Niemann CU, Kater AP, Gregor M, Hallek M, Jerkeman M, Buske C; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. ESMO Clinical Practice Guideline interim update on new targeted therapies in the first line and at relapse of chronic lymphocytic leukaemia. Ann Oncol. 2024 Sep;35(9):762-768. doi: 10.1016/j.annonc.2024.06.016. Epub 2024 Jul 3. No abstract available.
PubMed 38969011Eichhorst B, Fink AM, Bahlo J, Busch R, Kovacs G, Maurer C, Lange E, Koppler H, Kiehl M, Sokler M, Schlag R, Vehling-Kaiser U, Kochling G, Ploger C, Gregor M, Plesner T, Trneny M, Fischer K, Dohner H, Kneba M, Wendtner CM, Klapper W, Kreuzer KA, Stilgenbauer S, Bottcher S, Hallek M; international group of investigators; German CLL Study Group (GCLLSG). First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016 Jul;17(7):928-942. doi: 10.1016/S1470-2045(16)30051-1. Epub 2016 May 20.
PubMed 27216274
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Multicenter, Prospective Phase II Clinical Trial of Delayed Fixed-duration Combination With Sotoraclax Following Zanubrutinib Induction in Patients With CLL/SLL: Stop Trial 2.0
- ClinicalTrials.gov ID
- NCT07682415
- Acronym / sponsor ID
- ZS / IIT2026068
- Conditions
- CLL / SLL
- Keywords
- Zanubrutinib, Sonrotoclax, Chronic Lymphocytic Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Yi ShuhuaUniversity, hospital or other
- Collaborators
- BeOne Medicines
- Study start
- 8 Jun 2026 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 1 Aug 2034 (estimated)
- First posted
- 2 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if zanubrutinib induction followed by delayed fixed-duration combination with sonrotoclax works to treat previously untreated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL). It will also learn about the safety of this combination regimen. The main questions it aims to answer are:Does this combination therapy achieve undetectable minimal residual disease (uMRD) in participants?What medical problems (adverse events) do participants have when taking zanubrutinib and sonrotoclax?Researchers will conduct a single-arm study to systematically evaluate the MRD clearance, efficacy, safety, and immune-related functions of this specific treatment sequence.Participants will:Low-risk group (without 17p deletion/TP53 mutation): Take zanubrutinib monotherapy for 12 cycles, followed by combination zanubrutinib + sonrotoclax for 12 cycles, then discontinue treatment for observation.High-risk group (with 17p deletion/TP53 mutation): Follow the same initial regimen (12 cycles monotherapy + 12 cycles combination), followed by zanubrutinib monotherapy maintenance until disease progression.Visit the clinic periodically for MRD assessment (via flow cytometry), efficacy evaluation (CT/PET-CT, lab tests), and safety checks (physical exam, blood tests, ECG).Undergo immune function evaluation via peripheral blood samples to assess changes in T-cell counts and subsets.
Detailed description
This exploratory Phase II single-arm clinical trial is designed to evaluate the efficacy, safety, and immune reconstitution effects of a novel delayed fixed-duration BTK inhibitor (BTKi) induction followed by BCL-2 inhibitor combination regimen in previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients, with risk-stratified post-treatment management based on TP53/del(17p) status.Scientific RationaleCLL/SLL is a mature B-cell clonal proliferative neoplasm, where traditional chemoimmunotherapy has limited efficacy and high toxicity in high-risk populations with del(17p)/TP53 mutations. The current treatment paradigm has shifted to targeted therapies, with BTKi + BCL-2i combination as a first-line strategy. However, existing BCL-2i-based fixed-duration regimens have a grade ≥3 treatment-emergent adverse event (TEAE) incidence of 45%-80%, primarily hematological toxicities and infections. Prior clinical evidence shows that 12 cycles of BTKi monotherapy induction before combination therapy (the "brake" regimen) reduces infection risk compared to alternating chemoimmunotherapy + BTKi regimens, and 12 months of BTKi monotherapy increases T-cell receptor diversity, correlating with better clinical response and lower infection rates in relapsed/refractory CLL. This supports that extending BTKi induction before fixed-duration BCL-2i combination may optimize immune reconstitution, improving safety and long-term disease control.The study uses two investigational agents: zanubrutinib, a next-generation highly selective BTKi with higher BTK target selectivity and fewer off-target effects (e.g., lower cardiovascular adverse event risk vs. first-generation ibrutinib) compared to ibrutinib, approved in China for relapsed/refractory CLL/SLL and mantle cell lymphoma (MCL); and sonrotoclax, a highly selective BCL-2 inhibitor that restores mitochondrial apoptosis in CLL cells, with monotherapy showing 80.5% ORR and 26.8% CR/CRi rate in BTKi-pretreated high-risk relapsed/refractory CLL, and zanubrutinib + sonrotoclax combination achieving 92% 48-week uMRD rate and 100% 30-month PFS rate in treatment-naïve CLL/SLL. Study Design and PopulationThe study will consecutively enroll approximately 60 treatment-naïve CLL/SLL subjects meeting the 2025 Chinese CLL/SLL Diagnosis and Treatment Guidelines criteria, stratified into two groups:High-risk group (n=20): With 17p deletion (del17p) and/or TP53 mutationLow-risk group (n=40): Without del17p and/or TP53 mutationLow-risk group: Discontinue all treatment and enter observational follow-upHigh-risk group: Receive zanubrutinib monotherapy maintenance until disease progressionThis protocol is designed to systematically evaluate whether the delayed BCL-2i combination after extended BTKi induction improves MRD clearance, reduces toxicity, and optimizes long-term outcomes in treatment-naïve CLL/SLL, with tailored post-treatment management for high-risk populations to address their higher relapse risk.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-risk group（Without del17p and/or TP53 mutation） | Experimental | Drug: 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax12 cycles of zanubrutinib monotherapy induction → 12 cycles of zanubrutinib combined with sonrotoclax → discontinuation of study drugs followed by regular follow-up |
| High-risk group(With del17p and/or TP53 mutation) | Experimental | Drug: 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax, Drug: zanubrutinib maintenance until disease progression12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax, then zanubrutinib maintenance monotherapy until disease progression or intolerable toxicity occurs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Aged ≥18 years, no restriction on gender.
- Newly diagnosed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) consistent with the Chinese Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (2025 Edition).
- Meet at least one of the following indications for CLL treatment:
- ③ Unexplained fever >38.0 °C lasting ≥2 weeks without confirmed infection;
- ④ Unexplained night sweats persisting for more than 1 month without confirmed infection.
Key exclusion criteria (13 listed)
- 1. Previously received any systemic anti-tumor therapy for CLL/SLL. 2. Pathologically confirmed transformation to Richter's syndrome via biopsy. 3. Severe non-lymphoma-related hepatic or renal impairment defined as: ALT/AST >3×ULN or TBIL >2×ULN; creatinine clearance <30 mL/min or serum creatinine >2×ULN.
- 4. Significant pre-existing renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular or hepatic disease judged by the investigator to compromise trial participation.
- 5. Other uncontrolled clinically significant medical conditions including but not limited to:
- 7. Received major surgery (excluding lymph node biopsy) within 14 days prior to enrollment or scheduled to undergo major surgery during trial treatment.
- 8. Inability to swallow capsules, malabsorption syndrome, or severe gastrointestinal disorders including prior gastrectomy, small bowel resection, symptomatic inflammatory bowel disease, ulcerative colitis, partial or complete intestinal obstruction.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax12 cycles of zanubrutinib monotherapy induction → 12 cycles of zanubrutinib combined with sonrotoclax → discontinuation of study drugs followed by regular follow-up Zanubrutinib Dosage The total daily oral dose is 320 mg. The dosing schedule is 160 mg (2 × 80 mg capsules) twice daily, Sonrotoclax Dose Escalation Schedule Cycle 13 Week 1 (C13W1): Days 1-3: 1 mg daily (1 × 1 mg tablet); Days 4-7: 2 mg daily (2 × 1 mg tablets) Cycle 13 Week 2 (C13W2): Days 1-3: 5 mg daily (1 × 5 mg tablet); Days 4-7: 10 mg daily (2 × 5 mg tablets) Cycle 13 Week 3 (C13W3): Days 1-3: 20 mg daily (1 × 20 mg tablet); Days 4-7: 40 mg daily (2 × 20 mg tablets) Cycle 13 Week 4 (C13W4): Days 1-3: 80 mg daily (1 × 80 mg tablet); Days 4-7: 160 mg daily (2 × 80 mg tablets) Cycle 14 Week 1 (C14W1) and all subsequent cycles: 320 mg daily (4 × 80 mg tablets) | Drug | High-risk group(With del17p and/or TP53 mutation), Low-risk group（Without del17p and/or TP53 mutation） |
| zanubrutinib maintenance until disease progressionContinuous zanubrutinib monotherapy until disease progression or intolerable toxicity occurs. | Drug | High-risk group(With del17p and/or TP53 mutation) |
Primary outcome
uMRD rate
Time frame: At the end of 12 cycles (each cycle is 28 days) of combination therapy
Proportion of patients achieving undetectable minimal residual disease (uMRD, defined as MRD <10-⁴, fewer than 1 CLL cell per 10,000 leukocytes)
5 secondary outcomes
Objective Response Rate
Time frame: At the end of 12 cycles (each cycle is 28 days) of combination therapy
Complete Response Rate
Time frame: At the end of 12 cycles (each cycle is 28 days) of combination therapy
Duration of Response
Time frame: up to 8 years
Progression-Free Survival
Time frame: up to 8 years
Overall Survival
Time frame: up to 8 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
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- Background: PubMed 32702320Laurencin CT, Walker JM. A Pandemic on a Pandemic: Racism and COVID-19 in Blacks. Cell Syst. 2020 Jul 22;11(1):9-10. doi: 10.1016/j.cels.2020.07.002. Epub 2020 Jul 22.
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- Individual participant dataSharing planned: Yes. only IPD used in the results publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tingyu Wang, Doctor contact
Shuhua Yi, Docter principal investigator
Blood Disease Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, CAMS)
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 12 cycles of zanubrutinib followed by 12 cycles of zanubrutinib in combination with sonrotoclax and zanubrutinib maintenance until disease progression in people with CLL / SLL, run by Yi Shuhua at 7 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shuhua Yi, Doctor (（+86）15900265415, yishuhua@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
uMRD rate (time frame: At the end of 12 cycles (each cycle is 28 days) of combination therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07682415, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.